This K23 award will allow Dr. Beckman, the first American Indian (AI) adult endocrinologist in the nation, to become an investigator proficient in interdisciplinary research using functional magnetic resonance imaging (fMRI) to study the causes of obesity. She has a career interest in the neuropsychology of obesity and diabetes and her focus is on the AI population in Minnesota. Obesity is a major health disparity in AIs, yet litle work is being done to unravel the neurobiology of this problem. The training and research activities will allow her to examine the complexities of computational neuroscience, functional neuroanatomy, and the contribution of opioidergic neurons to brain reward pathways. The application proposes an intensive, 5-year program of mentored research and formal training activities to enhance Dr. Beckman's skills and experience in: 1) clinical research methods and biostatistics, 2) technical aspects of fMRI data acquisition and analysis, and 3) role of opioidergic neurons in the neuroendocrine regulation of appetite. In the long term, Dr. Beckman will apply these translational research skills to study neuromodulation, cognitive restructuring, and opioid antagonists as potentially effective treatments for the public health problem of obesity in her AI patients who may be hyperresponsive to environmentally rewarding food cues. The research component of this career development award targets the neurobiology of behavioral responses to food in 60 AIs. The specific aims are to: 1) use fMRI to compare brain activation associated with the response to visual food cues in obese versus lean AI women, 2) use fMRI to compare the effects of naltrexone, an opioid antagonist, versus placebo, on brain activation associated with response to palatable food cues, 3) compare the effects of naltrexone versus placebo on food intake in obese and lean AI women, by measuring calories consumed. The University of Minnesota is an exceptional environment for Dr. Beckman to gain the skills needed to achieve her goals. The training component uses academic resources including the Division of Diabetes, Metabolism, and Endocrinology, Minnesota Obesity Center, Center for the Study of Impulsivity in Addiction, Center for Magnetic Resonance Imaging, and Clinical and Translational Science Institute. Dr. Beckman's mentors are highly regarded scientists in the areas of obesity, addiction, and neuroimaging. PUBLIC HEALTH RELEVANCE: Despite the disproportionate obesity burden among AIs, this will be the first study using fMRI and an opioid antagonist to focus on this underrepresented population. Our results will provide important data about brain activation in response to high-calorie foods that will inform dietary interventions aimed at preventing and treating obesity and may identify a promising pharmacologic treatment for obesity and overeating in AIs.